Analysing the pH-dependent properties of proteins using pKa calculations

Journal of Molecular Graphics and Modelling

Volumn 25, Issue 5, 2007, Pages 691-699

  Nielsen, Jens Erik ^a  

^a University College Dublin   (Ireland)

Author keywords

Enzyme active site electrostatics; pKa value decomposition; Protein pKa calculations; Protein stability

Indexed keywords

CATALYSIS; ELECTROSTATICS; GRAPHICAL USER INTERFACES; PH EFFECTS; RELIABILITY;

ENZYME ACTIVE SITES; PROTEIN STABILITY; TITRATABLE GROUPS;

PROTEINS;

PROTEIN;

ARTICLE; CALCULATION; CATALYSIS; PH; PKA; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN STABILITY; PROTEIN STRUCTURE; RELIABILITY;

ALPHA-AMYLASE; ANIMALS; BINDING SITES; COMPUTER SIMULATION; DRUG STABILITY; ELECTROSTATICS; HYDROGEN-ION CONCENTRATION; MODELS, CHEMICAL; MURAMIDASE; PROTEINS; SOFTWARE;

EID: 33846614924     PISSN: 10933263     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmgm.2006.05.007     Document Type: Article

References (47)

1. Gunner M.R., et al. Backbone dipoles generate positive potentials in all proteins: origins and implications of the effect. Biophys. J. 78 3 (2000) 1126-1144
2. Nielsen J.E., and Vriend G. Optimizing the hydrogen-bond network in Poisson-Boltzmann equation-based pK(a) calculations. Proteins 43 4 (2001) 403-412
3. Antosiewicz J., McCammon J.A., and Gilson M.K. Prediction of pH-dependent properties of proteins. J. Mol. Biol. 238 3 (1994) 415-436
4. a values of ionizable groups in bacteriorhodopsin. J. Mol. Biol. 224 2 (1992) 473-486
5. Mehler E.L., and Guarnieri F. A self-consistent, microenvironment modulated screened coulomb potential approximation to calculate pH-dependent electrostatic effects in proteins. Biophys. J. 77 1 (1999) 3-22
6. a calculations: conformational averaging versus the average structure. Proteins 33 2 (1998) 145-158
7. as in proteins. Proteins 15 3 (1993) 252-265
8. Li H., Robertson A.D., and Jensen J.H. Very fast empirical prediction and rationalization of protein pK(a) values. Proteins 61 4 (2005) 704-721
9. Mongan J., Case D.A., and McCammon J.A. Constant pH molecular dynamics in generalized Born implicit solvent. J. Comput. Chem. 25 16 (2004) 2038-2048
10. Alexov E.G., and Gunner M.R. Incorporating protein conformational flexibility into the calculation of pH-dependent protein properties. Biophys. J. 72 5 (1997) 2075-2093
11. as and adding missing hydrogens to macromolecules. Nucl. Acids Res. 33 (2005) pW368-pW371 (Webserver issue)
12. a values, Nucl. Acids Res. (in press).
13. Lamotte-Brasseur J., Dubus A., and Wade R.C. pK(a) calculations for class C beta-lactamases: the role of Tyr-150. Proteins 40 1 (2000) 23-28
14. Tolbert B.S., et al. The active site cysteine of ubiquitin-conjugating enzymes has a significantly elevated pK(a): functional implications. Biochemistry 44 50 (2005) 16385-16391
15. Synstad B., Gaseines S., Aalten D.M.F., Vriend G., Nielsen J.E., and Eijsink V.G.H. Mutational and computational analysis of the role of conserved residues in the active site of a family 18 chitinase. Eur. J. Biochem. 271 2 (2004) 253-262
16. a calculations. Protein Sci. 12 2 (2003) 313-326
17. Mock W.L., and Stanford D.J. Arazoformyl dipeptide substrates for thermolysin. Confirmation of a reverse protonation catalytic mechanism. Biochemistry 35 23 (1996) 7369-7377
18. Joshi M.D., et al. Hydrogen bonding and catalysis: a novel explanation for how a single amino acid substitution can change the pH optimum of a glycosidase. J. Mol. Biol. 299 1 (2000) 255-279
19. a of the general acid/base carboxyl group of a glycosidase cycles during catalysis: a 13C NMR study of bacillus circulans xylanase. Biochemistry 35 31 (1996) 9958-9966
20. Alexov E. Calculating proton uptake/release and binding free energy taking into account ionization and conformation changes induced by protein-inhibitor association: application to plasmepsin, cathepsin D and endothiapepsin-pepstatin complexes. Proteins 56 3 (2004) 572-584
21. Tanford C. Protein denaturation. Part C. Theoretical models for the mechanism of denaturation. Adv. Protein Chem. 25 (1970) 1-95
22. Beroza P., et al. Protonation of interacting residues in a protein by a Monte Carlo method: application to lysozyme and the photosynthetic reaction center of Rhodobacter sphaeroides. Proc. Natl. Acad. Sci. USA 88 13 (1991) 5804-5808
23. Tanford C., and Roxby R. Interpretation of protein titration curves. Application to lysozyme. Biochemistry 11 (1972) 2193-2198
24. a, proton transfer reactions, and general acid catalysis reactions in enzymes. Biochemistry 20 11 (1981) 3167-3177
25. Klapper I., et al. Focusing of electric fields in the active site of Cu-Zn superoxide dismutase: effects of ionic strength and amino-acid modification. Proteins 1 1 (1986) 47-59
26. Onufriev A., Bashford D., and Case D.A. Modification of the generalized Born model suitable for macromolecules. J. Phys. Chem. B 104 (2000) 3712-3720
27. Feig M., et al. Performance comparison of generalized Born and Poisson methods in the calculation of electrostatic solvation energies for protein structures. J. Comput. Chem. 25 2 (2004) 265-284
28. Ondrechen M.J., Clifton J.G., and Ringe D. THEMATICS: a simple computational predictor of enzyme function from structure. Proc. Natl. Acad. Sci. USA 98 22 (2001) 12473-12478
29. Onufriev A., Case D.A., and Ullmann G.M. A novel view of pH titration in biomolecules. Biochemistry 40 12 (2001) 3413-3419
30. Ko J., et al. Statistical criteria for the identification of protein active sites using theoretical microscopic titration curves. Proteins 59 2 (2005) 183-195
31. Schutz C.N., and Warshel A. What are the dielectric "constants" of proteins and how to validate electrostatic models?. Proteins 44 4 (2001) 400-417
32. Alexov E. Role of the protein side-chain fluctuations on the strength of pair-wise electrostatic interactions: comparing experimental with computed pK(a)s. Proteins 50 1 (2003) 94-103
33. a values in enzyme active sites. Protein Sci. 12 (2003) 1894-1901
34. a calculations through flexibility based sampling of a water-dominated interaction scheme. Protein Sci. 13 10 (2004) 2793-2805
35. Elcock A.H. Realistic modeling of the denatured states of proteins allows accurate calculations of the pH dependence of protein stability. J. Mol. Biol. 294 4 (1999) 1051-1062
36. a predictions. J. Mol. Biol. 267 4 (1997) 1002-1011
37. Wlodek S.T., Antosiewicz J., and McCammon J.A. Prediction of titration properties of structures of a protein derived from molecular dynamics trajectories. Protein Sci. 6 2 (1997) 373-382
38. as of ionizable residues in proteins: semi-microscopic and microscopic approaches. J. Phys. Chem. 101 (1997) 4458-4472
39. Nielsen J.E., and Borchert T.V. Protein engineering of bacterial alpha-amylases. Biochim. Biophys. Acta 1543 2 (2000) 253-274
40. a values (submitted for publication).
41. Linderstrom-Lang K. Om proteinstoffernes ionisation. Compt. Rend. Trav. Lab. Carlsberg 15 7 (1924) 1-29
42. Kim J., Mao J., and Gunner M.R. Are acidic and basic groups in buried proteins predicted to be ionized?. J. Mol. Biol. 348 5 (2005) 1283-1298
43. Alexov E. Numerical calculations of the pH of maximal protein stability. The effect of the sequence composition and three-dimensional structure. Eur. J. Biochem. 271 1 (2004) 173-185
44. G.V. Rossum, Python, 2003.
45. Vriend G. WHAT IF: a molecular modeling and drug design program. J. Mol. Graph. 8 1 (1990) 52-56, 29
46. Yang A.S., and Honig B. On the pH dependence of protein stability. J. Mol. Biol. 231 2 (1993) 459-474
47. A values of the denatured state are on average 0.4 units lower than those of model compounds. Biochemistry 34 29 (1995) 9424-9433